This application is a competing continuation of MH-R01 53735, "Prevention of Recurrent Postpartum Major Depression". The original study was a randomized clinical trial of immediate post-birth antidepressant administration to prevent the recurrence of postpartum-onset depression (PPMD) in women who had previous episodes of PPMD. The major findings were that the tricyclic antidepressant nortriptyline (NTP) was equivalent to placebo (PL) in preventive efficacy. However, the serotonin selective reuptake inhibitor sertraline (SERT) was significantly more efficacious than placebo in the same preventive treatment model. The primary aim of the proposed study is to test the efficacy of SERT for the prevention of PPMD in a broader population of women. SERT was determined to be efficacious for the prevention of PPMD in women who had previous episodes specifically of PPMD; therefore, all subjects had at least one child. We will replicate the successful SERT vs PL study with an expanded population of subjects. Women who have had at least one episode of MD prior to the index pregnancy will be included. We will also determine the optimal duration of preventive therapy. During the previous study, SERT was tapered and discontinued at from weeks 17-20. The protection against recurrence was quickly lost, and the risk approached that of the PL-treated group. Therefore, the period of preventive therapy will be extended to the 24 weeks. We will re-randomize the women who respond to SERT at 24 weeks to either continued SERT or PL in order to assess both the durability of and necessity for longer-term preventive therapy. We will evaluate the effects of SERT exposure to infants through breast milk on pediatric and developmental outcomes at one year. Monitoring procedures included mother and infant serum antidepressant levels. Developmental evaluations of infants through 12 months of age will be performed. Maternal MD, an exposure that clearly has a negative impact upon several aspects of child development, also will be considered as an exposure with effects on child outcomes.